CD4 T cell responses to Chlamydia infection

CD4 T 细胞对衣原体感染的反应

• 批准号: 9027019
• 负责人: STEPHEN J MCSORLEY
• 金额: $ 38.43万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9027019
• 关键词: Adjuvant; Affect; Animal Model; Antibiotic Therapy; Antigens; Bacteria; Bacterial Antigens; Bacterial Infections; Blindness; CD4 Positive T Lymphocytes; Cells; Cellular biology; Centers for Disease Control and Prevention (U.S.); Cervix Uteri; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Clinical Research; Consensus; Data; Development; Disease; Ectopic Pregnancy; Female; Flagellin; Generations; Genital system; Health; Heterogeneity; Human; Imagery; Immune; Immunity; Immunization; Incidence; Individual; Infection; Infertility; Knowledge; Laboratories; MHC Class II Genes; Mediating; Mediator of activation protein; Memory; Modeling; Mucous Membrane; Mus; Nature; Pathology; Pelvic Inflammatory Disease; Population; Primary Infection; Process; Reagent; Regulatory T-Lymphocyte; Reporting; Route; Scientist; Sexually Transmitted Diseases; Specificity; Surface; T cell response; T-Lymphocyte Subsets; Testing; Tissues; Vaccines; Woman; adaptive immunity; aged; base; chronic pelvic pain; memory CD4 T lymphocyte; mouse model; public health relevance; reproductive; reproductive tract; response; secondary infection; sexually active; young woman

 DESCRIPTION (provided by applicant) Chlamydia infections are a cause of blindness worldwide and a major cause of sexually transmitted disease in the US. Greater understanding of protective immunity to Chlamydia at mucosal surfaces is urgently required if an effective vaccine is to become a reality. Our application will examine fundemental aspects of protective CD4 T cells during infection of the female reproductive tract mucosa. Our experimental approach is unique in that it utilizes a natural route of infection, uses an established model where CD4 T cells participate in bacterial clearance, and allows for direct visualization of endogenous Chlamydia-specific CD4 T cells using reagents that were recently developed in our laboratory. Our application specifically proposes to, (i) examine CD4 T cell heterogeneity and the contribution of these heterogeneous responses to protection and pathology, (ii) examine whether antibiotic-treatment adversely affects the development of protective TRM cells in the reproductive tract mucosa, (iii) determine whether the use of flagellin can enhance moderate protective immunity elicited by the single antigen PmpG1. Understanding each of these issues will increase our knowledge of Chlamydia-specific CD4 T cell biology and may be vitally important for the generation of a new Chlamydia vaccine.

 说明(申请人提供)衣原体感染是全世界失明的原因，也是美国性传播疾病的主要原因。如果一种有效的疫苗要成为现实，迫切需要更多地了解黏膜表面对衣原体的保护性免疫。我们的应用程序将检查在女性生殖道粘膜感染期间保护性CD4T细胞的基本方面。我们的实验方法是独特的，因为它利用了一种自然的感染途径，使用了已建立的CD4T细胞参与细菌清除的模型，并允许使用我们实验室最近开发的试剂直接显示内源性衣原体特异性CD4T细胞。我们的应用特别建议：(I)检测CD4T细胞的异质性以及这些异质性反应对保护和病理的贡献，(Ii)检查抗生素治疗是否对生殖道粘膜中保护性TRM细胞的发育产生不利影响，(Iii)确定鞭毛的使用是否可以增强由单一抗原PmpG1引发的中等保护性免疫。了解这些问题中的每一个都将增加我们对衣原体特异性CD4T细胞生物学的了解，并可能对新衣原体疫苗的产生至关重要。